Recent work from our laboratory (Okarma, T.B., Krueger, J.A., and Holman, H.R., 1981 J.C.I., submitted), and others, (Lerner, M.R., et al, Nature 283:220, 1980; and Rogers and Wall, P.N.A.S. 77:1877, 1980), suggests a possible role for the RNP and Sm antigens (components of the extractable nuclear antigen) in heterogenous nuclear RNA (hnRNA) processing. Antibodies from lupus sera precipitate a set of seven nuclear proteins and a series of small nuclear RNAs (snRNAs), one of which (U1) exhibits complementarity at its 5' end to those nucleotide sequences across splice junctions of hnRNA molecules. Furthermore, antibodies to the U1 snRNA inhibit processing in vitro. A major obstacle to the study of the functional characteristics of these antigens is that their isolation involves immunoprecipitation or denaturation, and results in small yields. The preparative electrofocusing methods developed in our laboratory isolate these antigens in milligram quantities in undenatured form, facilitating the analysis of their biological properties. We have prepared milligram quantities of the antigen from rat GH3 cells in itro and have characterized a nick translation system for cloned growth hormone (GH) genomic DNA (gDNA) and cDNA derived from this same cell system. Using these techniques, we first wish to explore these snRNAs isolated from the Sm and RNP antigens for binding to intron-exon boundaries in cloned fragments of growth hormone gDNA using 1) Northern electroblot techniques, and 2) solution RNA DNA hybridization with S1 nuclease digestion ad R loop mapping. If specific binding is detected, we would then analyze intact Sm and RNP antigen fractions for RNA "splicease" activity in a cell-free growth hormone hnRNP processing system using these same cloned growth hormone genes as hybridization probes. The demonstration of processing activity would be significant because we could use our present techniques to isolate these antigens in milligram quantities and employ them to splice RNA copied from genomic DNA sequences that could be cloned in any expression plasmid.